Gislin Dagnelie, Ph.D., is an Associate Professor of Ophthalmology in the Johns Hopkins University School of Medicine and the associate director of the Lions Vision Research and Rehabilitation Center, a division of the Johns Hopkins Wilmer Eye Institute. His work over the last 20 years has been supported by grants from the National Institutes of Health, National Science Foundation, Foundation Fighting Blindness, and several companies developing ophthalmic devices and visual prosthetics.

Dr. Dagnelie is a native of the Netherlands, where he earned a Ph.D. in medical physics at the University of Amsterdam. In 1986, he came to the Wilmer Eye Institute for research in retinitis pigmentosa, an interest he is pursuing to this day.

He has been the Center Principal Investigator (PI) for clinical trials of the Optobionics Artificial Silicon Retina (2004-2007) and the Second Sight Argus™ II retinal implant (2007-present). Since the clinical introduction of the Argus II in early 2014, Dr. Dagnelie has been managing the retinal implant program at Johns Hopkins, and acted as the Center PI for several follow-up studies of Argus II use in patients' daily lives. His principal research effort is in understanding and measuring to what extent individuals with minimal vision can make effective use of that vision.

His involvement with prosthetic [i.e., artificial] vision began in 2004 with a product developed by Optobionics. Since 2009, Dr. Geruschat has been involved with Second Sight Medical Products, Inc., helping them to develop functional assessments and a rehabilitation curriculum that low vision therapists and orientation and mobility instructors can use when teaching patients to use the Argus II Retinal Prosthesis System.

Some Background on Restored Vision

During the past several years, there has been much "buzz" in the popular press about the capabilities of the so-called "bionic" eye, described variously as "miraculous," "restoring sight," and "letting me see again." At VisionAware, we have followed the development of "bionic" or "prosthetic" vision closely, avoiding hyperbole and striving to report factual, research-based information about the limitations of restored vision.

They draw on their shared background in the rehabilitation of native low vision [i.e., vision loss resulting from age-related macular degeneration, diabetes, glaucoma, and retinitis pigmentosa, for example] and of restored vision, comparing and contrasting traditional rehabilitation for low vision with a new challenge: rehabilitation of restored low vision following decades of blindness.

The Argus II was developed by Second Sight Medical Products, Inc., of Lausanne, Switzerland and Sylmar, California to treat adults with severe to profound retinitis pigmentosa (RP). It consists of the following components: (a) a small video camera, (b) a transmitter mounted on a pair of eyeglasses, (c) a video processing unit (VPU), and (d) an artificial retina (the implanted retinal prosthesis, which is an array of electrodes).

Maureen Duffy: Hello Dr. Dagnelie and Dr. Geruschat. Thank you very much for taking the time to speak with us about your research in restored vision and your work with the Argus II Retinal Prosthesis System. To start, can you tell our readers more about "restored vision," including how it differs from low vision?

Gislin Dagnelie: When we talk about restored vision, it suggests we can repair the retina to do all the things it previously did, with rods and cones that make the right connections to secondary cells, known as bipolar cells, and those in turn making connections to the retinal ganglion cells that send signals to the brain.

Components of the Argus IIRetinal Prosthesis System

Unfortunately, that's not how it works. The electrodes on the implant stimulate the bipolar cells and ganglion cells, but they don't make distinctions about which cells they are stimulating. It's like trying to play a melody on the piano wearing boxing gloves. As a result, restored vision looks very different from native vision, more like blurry shadows moving around, and learning to understand this blurry vision takes a lot of practice.

Duane Geruschat: Prosthetic vision, specifically from a retinal chip implant, is flashing lights and possibly light patterns. This is potentially dramatically different from severely reduced native vision where you may see shadows, contrast, brightness, and motion. The light stimulation provided by a retinal implant has little, if any, relationship to what you have stored in your visual memory. Recipients are most likely developing new visual memories of things they are viewing.

MD: I'm also interested to know more about your backgrounds, including how you came to be involved in low vision – and now restored vision – research.

Gislin Dagnelie: I'm a physicist by training, but I specialized in a sub-field called medical physics, that is, applying the models and measurement methods used by physicists to understanding the human body and senses. In 1986 I came to Johns Hopkins from the University of Amsterdam and joined a research project trying to understand how vision changes in retinitis pigmentosa and other types of retinal degeneration. Our current work with retinal implants stems from that research, spurred on by advances in micro-electronics and retinal surgery.

Duane Geruschat: My background is in orientation and mobility as a Certified Orientation and Mobility Specialist (COMS) and in low vision as a Certified Low Vision Therapist (CLVT). I began my career working in a low vision clinic, doing traditional low vision optical device instruction and environmental modifications. Gradually, I moved into research and have spent the past 25 years as a full-time researcher, mostly in the area of low vision and mobility.

I have spent a lot of time on street corners, monitoring eye movements of pedestrians with low vision as they try to cross the street and I have done a lot of work with the perceptual judgements we humans have to make to determine if we have enough time to cross the street prior to the arrival of an oncoming car. For the past decade I've become more and more involved with retinal implants, having supported the development of functional assessments, instructional curricula, and continuing education programs for service providers.

MD: In your article, you discuss the psychology of vision restoration, including how the simple phrase "I can see again" has a variety of meanings for people who have experienced restored vision via the Argus II. Can you elaborate on that for our readers?

A user of the Argus IIRetinal Prosthesis System

Gislin Dagnelie: I think of restored vision as a very personal and emotional experience. For some, it may be the sense of independence that even a little bit of sight gives them, like seeing crosswalk lines; for others, it is the social aspect of being able to locate people walking by. Almost every Argus II user can give you an example like that, something that really brought home the impact of even a little vision that had been missing for years.

Duane Geruschat: Retinitis pigmentosa (RP) is a unique condition, in that there is no medical treatment, it is progressive, and it ultimately leads to blindness. Patients live with this information and the experience of losing their sight over many decades. The average Argus II user has been blind for 15 years. With no expectation of ever seeing anything again, even the limited vision provided by the Argus II can have major impact on a person. The phrase "I can see again" says nothing about what they see or how they use it; instead, it is the emotional response from someone with the life history that I just described. Seeing again with no expectation of ever seeing again is a powerful experience for many of these users.

MD: I was also interested to read this: "...the reintroduction of sight can be experienced by some people as a 'resetting of the clock,' an experience that returns them to a world with limited visual input following years of total blindness. One of the key consequences of this timeline is that the reintroduction of ultra-low vision results in the vision becoming a supplement to blindness skills for the purpose of enhancing independence." What is "ultra-low vision," exactly?

Gislin Dagnelie: Most people who have low vision can still use their vision for some tasks, either to get around, or to see large objects and read with high magnification. When we use the term ultra-low vision, we are referring to people who can still tell light from dark, maybe tell where the light is coming from, or see moving lights or shapes. But they can't really tell what the shapes are, unless they have some other information: sound, smell, touch, context. If you're standing on a subway platform, you don't need much vision to see the train roll in and come to a stop, and you may be able to tell where the open doors are.

Duane Geruschat: For the reader who is a provider of blindness services, you know that at times it is difficult to teach blindness skills because the person is struggling to use their vision. The remaining vision can, at times, make it more difficult to do activities of daily living. So we in blind rehabilitation seek out environments and tasks where the remaining vision cannot be used, so as to teach non-visual skills.

This can be challenging because the person often experiences this as "taking away their vision" and they aren't happy. By way of comparison, the user of the Argus II has been functionally blind for over a decade. Most have had a full course of blind rehabilitation and can accomplish most tasks of daily living with no eyesight. Now we are reintroducing a small amount of eyesight, but the difference here is that the person has good blindness skills so we are now trying to figure out how to incorporate this new eyesight with good blindness skills, while what we are used to doing is teaching blindness skills to someone who is losing eyesight.

MD: Can you give us an update on the status of the Argus II development? And what next steps may be on the horizon for vision restoration in general?

Gislin Dagnelie: The Argus II is limited by the large size of the electrodes, compared to the scale of the retinal cells it is stimulating, so it's not going to get dramatically better. But some improvements are possible – for example, seeing a little more detail, or better defined shapes – especially by combining the stimulation from different electrodes in different ways. Some changes to accomplish that are already in the works.

As for vision restoration in general: Everyone talks about gene therapy and stem cells, both of which would actually repair the network of cells in the retina. Each of those approaches has limitations, and how severe those are will not be known until those approaches are used in patients. For gene therapy, it is already known that the results may wear off, and that the best results are obtained by treatments before a lot of vision is lost. Whatever approach you look at, it's likely to take several decades to become fully developed. The retina is an amazing network of many different kinds of cells, and restoring it once the network is broken up is extremely difficult, no matter what approach you use.

Duane Geruschat: I think of the future in the context of how people use the new vision. A larger visual field would be helpful. Right now the Argus II has a visual field of 18 degrees, which is quite small. As described by Dr. Dagnelie, it is doubtful they will be able to improve acuity by reducing the size of the electrode, but if they could increase the size of the visual field, then I would expect to see an impact on visual abilities. The great potential advantage of gene therapy and stem cell treatments is that the user would have vision that is potentially much more natural. While people certainly learn to interpret the light patterns of the Argus II, I assume that more natural vision would be preferred by most people.

MD: What do you regard as the next great frontier in vision science? I'm always interested in what practicing vision scientists have to say about the future of vision research.

Gislin Dagnelie: I'm actually very curious to see how well truly artificial vision can work; that is, computer-based analysis of the visual world that is good enough to steer robots or cars. Artificial vision exists, for very specific and limited tasks, but to make it good enough so it can support autonomous decision-making, that's a real challenge. Once it gets to that point, we may realize that restoring human vision is not as important as we thought it was, even though it will remain a dream worth pursuing.

Duane Geruschat: Most of the work in this field occurs from the eye itself to the optic nerve. This is where the actual damage to the eye has occurred. So the treatments are designed to minimize the impact of the eye disease. The reason for this, of course, is that it's easiest to address vision early in the process of seeing. The next big area of study may be in cortical stimulation. At least in theory, you could bypass the entire eye/optic nerve and provide the information directly to the visual cortex at the base of the brain. This is by far the most challenging approach, which is why few research groups are working on it, but over time this may be an exciting area of research for young researchers.

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